The rapid development of the pharmaceutical research and development (R&D) has brought new challenges to occupational health management, including the high uncertainty in the R&D process, emerging hazards, and compliance complexities associated with novel business models. Traditional management approaches exhibit limitations in effectively addressing the occupational health risks associated with these challenges. Based on the perspective of agile governance, this paper proposed an optimized pathway characterized by dynamic response, adaptive flexibility, and multi-stakeholder collaboration. It further offered countermeasures and recommendations from three aspects: concept renewal, mechanism innovation, and tool empowerment, aiming to provide reference for the effective management and control of occupational health risks in the innovation and development of the pharmaceutical R&D industry.

The transcriptome sequencing based on Illumina Novaseq 6000 Platform was performed with the untreated seed embryo(DS), stratified seed embryo(SS), and germinated seed embryo(GS) of Zanthoxylum nitidum, aiming to explore the molecular mechanism regulating the seed dormancy and germination of Z. nitidum and uncover key differentially expressed genes(DEGs). A total of 61.41 Gb clean data was obtained, and 86 386 unigenes with an average length of 773.49 bp were assembled. A total of 29 290 DEGs were screened from three comparison groups(SS vs DS, GS vs SS, and GS vs DS), and these genes were annotated on 134 Kyoto Encyclopedia of Genes and Genomes(KEGG) pathways. KEGG enrichment analysis revealed that the plant hormone signal transduction pathway is the richest pathway, containing 226 DEGs. Among all DEGs, 894 transcription factors were identified, which were distributed across 34 transcription factor families. These transcription factors were also mainly concentrated in plant hormone signal transduction and mitogen-activated protein kinase(MAPK) signaling pathways. Further real-time quantitative polymerase chain reaction(RT-qPCR) validation of 12 DEGs showed that the transcriptome data is reliable. During the process of seed dormancy release and germination, a large number of DEGs involved in polysaccharide degradation, protein synthesis, lipid metabolism, and hormone signal transduction were expressed. These genes were involved in multiple metabolic pathways, forming a complex regulatory network for dormancy and germination. This study lays a solid foundation for analyzing the molecular mechanisms of seed dormancy and germination of Z. nitidum.
Zanthoxylum/metabolism* ; Plant Dormancy/genetics* ; Seeds/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Transcriptome ; Gene Expression Profiling ; Germination ; Transcription Factors/metabolism* ; Plant Growth Regulators/genetics* ; Signal Transduction

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

The Guidelines for Occupational Hazard Assessment and Control of Active Pharmaceutical Ingredient in the Pharmaceutical Industry (T/WSJD 60—2024) is the first guiding standard in the field of health in China that focuses on occupational health protection for active pharmaceutical ingredient (API). It covers the general principles, work procedures, assessment methods, and control strategies for API occupational hazard assessment, providing practical guidance and recommendations for pharmaceutical enterprises to eliminate or reduce occupational health risks associated with API, improve working environment, and enhance refined management practices. This article interpreted and analyzed the background of standard establishment, formulation process, fundamental basis, and main content, to provide scientific and comprehensive technical support for occupational health managers in the pharmaceutical industry to better apply this standard.

Background Workers in printing jobs are exposed to a variety of organic solvents at low levels for a long period of time. Previous studies have focused on the main components in Material Safety Data Sheet or high-risk occupational hazardous agents, but have not been able to comprehensively and accurately identify the volatile organic compounds (VOCs) in printing jobs. Objective To qualitatively analyze the VOCs in ink, detergent, varnish, fountain solution, and other raw and auxiliary materials by headspace gas chromatography-mass spectrometry, and to accurately identify the occupational hazardous agents in printing jobs. Methods Raw and auxiliary materials used in printing jobs in 6 printing enterprises in Shanghai were sampled by headspace sampling, analyzed by gas chromatography-mass spectrometry, identified by National Institute of Standards & Technology ( NIST) Standard Library and retention time, and quantified by peak area percentage. Results A total of 181 VOCs were reported in the headspace of 25 organic solvent samples, with a total detection frequency of 337 items and 13.2±12.3 VOCs per sample. The most frequently detected VOCs category was naphthene, with a total of 69 items detected (22.5%), dominated by cyclohexane. The characteristics of VOCs components in the headspace of different types of samples were different. The largest number of VOCs was detected in the headspace of detergent samples, with an average of 31.5 VOCs detected. The characteristic components in detergent were aromatic hydrocarbons and ester compounds; alcohols were the characteristic components in varnish; and ester compounds were the characteristic components in ink. The results of cluster analysis showed that ethanol, toluene, ethyl acetate, cyclohexane, and acetone were occupational hazardous agents with high levels of exposure in printing jobs. Conclusion Many kinds of organic solvents used in printing process are difficult to identify by traditional methods. Headspace gas chromatography-mass spectrometry can help to accurately identify VOCs in the workplace, so as to more accurately assess the occupational hazards, and to provide a technical basis for guiding occupational health monitoring and implementing corresponding occupational health risk management and control.

Objective To explore the differential diagnostic indicators of adult-onset Still's disease(AOSD)from other fever of unknown origin(FUO).Methods The clinical data and laboratory indicators of 177 AOSD patients and 163 FUO patients who were hospitalized in the First Affiliated Hospital of Army Medical University from January 2010 to May 2021 were collected,and the patients were randomly divided into training group and verification group.Statistically significant variables were extracted from univariate analysis for receiver operating characteristic(ROC)curve analysis and the best cut-off value of the variables was obtained.The differential diagnostic indicators were extracted by multivariate logistic regression analysis and nomogram model was constructed.ROC curve,calibration curve,and decision curve analysis were used to evaluate the accuracy and stability of nomogram.Results Univariate analysis revealed that there were significant differences in 4 clinical features(arthralgia,rash,pharyngeal pain,myalgia)and 14 laboratory parameters[white blood cell count(WBC),monocyte percentage,neutrophil percentage,lymphocyte percentage,platelet count,C-reactive protein,interleukin-6(IL-6),ferritin,globulin,immunoglobulin A,and immunoglobulin G(IgG),creatine kinase,creatinine and complement C3].Multivariate analysis suggested that arthralgia,WBC≥9.995×109/L,IL-6≥98.13 ng/L,ferritin≥507.37 ng/ml,globulin≤36.58g/L,IgG≤13.59g/L,complement C3≥1.27 g/L were related with AOSD.The area under curve(AUC)values of training group and verification group were 0.917(95%CI 0.883-0.951)and 0.869(95%CI 0.802-0.936),respectively.The calibration curves showed good consistency.The decision curve analysis showed that training group and verification group had a large positive rate of return in the wide risk range of 5%-85%and 10%-85%,respectively.Conclusions This study has established a relatively accurate AOSD differential diagnosis model.The combination of arthralgia,WBC,IL-6,ferritin,globulin,IgG and complement C3 may help to distinguish AOSD from other causes of FUO.

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.